Abstract

Immune infiltrates in the tumor microenvironment (TME) of breast cancer (BRCA) have been shown to play a critical role in tumorigenesis, progression, invasion, and therapy resistance, and thereby will affect the clinical outcomes of BRCA patients. However, a wide range of intratumoral heterogeneity shaped by the tumor cells and immune cells in the surrounding microenvironment is a major obstacle in understanding and treating BRCA. Recent progress in single-cell technologies such as single-cell RNA sequencing (scRNA-seq), mass cytometry, and digital spatial profiling has enabled the detailed characterization of intratumoral immune cells and vastly improved our understanding of less-defined cell subsets in the tumor immune environment. By measuring transcriptomes or proteomics at the single-cell level, it provides an unprecedented view of the cellular architecture consist of phenotypical and functional diversities of tumor-infiltrating immune cells. In this review, we focus on landmark studies of single-cell profiling of immunological heterogeneity in the TME, and discuss its clinical applications, translational outlook, and limitations in breast cancer studies.

Highlights

  • Born in 2009 [1], selected as the Method of the Year 2013 by Nature Methods [2], the single-cell sequencing technologies are revolutionizing the details of whole-transcriptome and proteome snapshots from a tissue to a cell [3,4,5]

  • We explore ways in which other single-cell approaches, such as single-cell mass cytometry [10], that deepen our understanding of immunological responses and resistance in the tumor microenvironment, and examine potential future innovations in the field

  • This study uncovered a new role of complement in B-cell-dependent anti-tumor immunity and indicated that CD55 induced chemo-resistance by impeding the induction of inducible Tcell co-stimulator ligand (ICOSL)+ B cells and could be a potential therapeutic target to enhance the efficacy of immunogenic chemotherapy

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Summary

INTRODUCTION

Born in 2009 [1], selected as the Method of the Year 2013 by Nature Methods [2], the single-cell sequencing technologies are revolutionizing the details of whole-transcriptome and proteome snapshots from a tissue to a cell [3,4,5]. This study uncovered a new role of complement in B-cell-dependent anti-tumor immunity and indicated that CD55 induced chemo-resistance by impeding the induction of ICOSL+ B cells and could be a potential therapeutic target to enhance the efficacy of immunogenic chemotherapy. Their sub-stratified analysis and clinical conclusions should be validated in the future hypothesis-testing experimental investigation because of the small sample size examined in this study

CHARACTERIZING IMMUNE CELL HETEROGENEITY
Imaging mass cytometry
Findings
AUTHOR CONTRIBUTIONS
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